The general five-year survival rate for people with bladder cancer is 77%. Bladder cancer is highly treatable when it is diagnosed in the early stages. A new study by researchers at Northwestern Medicine offers hope as it demonstrates that an epigenetics drug currently being used for blood cancers and rare sarcomas may halt the growth of bladder cancer in mice by activating the immune system.
The new study is published in the journal Science Advances in a paper titled, “Immune activation is essential for the antitumor activity of EZH2 inhibition in urothelial carcinoma.”
Their findings are the first to demonstrate that a drug, tazemetostat, originally developed to treat lymphoma has been used to treat one of the most common solid tumors.
“We’ve discovered for the first time that the drug actually works by activating the immune system, not just by inhibiting the tumor,” explained lead study author Joshua Meeks, PhD, an associate professor of urology and of biochemistry and molecular genetics at Northwestern University Feinberg School of Medicine and a Northwestern Medicine physician/scientist.
“Survival for advanced bladder cancer is extremely poor, and the drug works by mechanisms different than any other therapy,” Meeks said. “This is the first application of epigenetic therapy in bladder cancer.”
The drug is a pill that is well tolerated and could be added to other systemic therapies in bladder cancer, Meeks said. It is now being tested in a national clinical trial led by investigators at Northwestern for patients with late-stage bladder cancer.
“EZH2 is commonly overexpressed in most solid tumors and works by ‘locking’ tumors in a state of growth,” Meeks said. “We think it’s one of the main genes involved in cancer. We were interested in that gene because the most common mutations in bladder cancer may make EZH2 more active. When cells have higher levels of this gene activity, they proliferate.”
When scientists knocked out EZH2 in bladder cancers in mice, the tumors were much smaller and packed with immune cells.
“That was our clue the immune system may be suppressed by EZH2,” Meeks said. “Next, we gave a commercially available drug (tazemetostat) to inhibit the activity of this gene. It caused a lot of immune cells to pack the bladder. Finally, when we used mice with no T cells, we found the drug was ineffective, confirming that the immune system was likely the primary pathway by which the drug works.”